US11313801B2 - Sample imaging apparatus - Google Patents

Sample imaging apparatus Download PDF

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Publication number
US11313801B2
US11313801B2 US16/581,694 US201916581694A US11313801B2 US 11313801 B2 US11313801 B2 US 11313801B2 US 201916581694 A US201916581694 A US 201916581694A US 11313801 B2 US11313801 B2 US 11313801B2
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sample
light
imaging
light source
tray
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US20200103349A1 (en
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Kohei Ota
Takuji Tada
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Fujifilm Corp
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Fujifilm Corp
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/06—Means for illuminating specimens
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/16—Microscopes adapted for ultraviolet illumination ; Fluorescence microscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/02—Mechanical
    • G01N2201/022—Casings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/02—Mechanical
    • G01N2201/023—Controlling conditions in casing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/08—Optical fibres; light guides

Definitions

  • the present invention relates to a sample imaging apparatus that irradiates a sample with light in a closed space to capture an image.
  • JP2015-177250A corresponding to U.S. Pat. No. 9,531,950B2
  • the sample which is a subject, a lens, a light source, and the like are arranged in a housing, whereby the sample is imaged.
  • a plane light source in which a light guide using a reflective diffusion plate and a transmission diffusion plate is formed, is used.
  • a sample imaging apparatus which images a sample such as biological molecules usually, performs imaging by arranging not only a sample as a subject but also a lens, a light source, and the like in a housing forming a closed space. Moreover, in order to appropriately perform analysis and the like, samples such as biological molecules have to be imaged on a certain environmental condition.
  • the temperature in the housing may rise and the state of the sample may change.
  • the type of light to be emitted to the sample is changed and imaging is performed a plurality of times, it takes a long time to complete the imaging. In such a case, the effect of the temperature change in the housing due to the heat generation of the light source is serious.
  • a sample imaging apparatus comprising: a housing that forms a closed space; a transparent tray on which a sample is placed in the housing; a plane light source that is formed by using a flat light guide plate, which propagates light emitted by a light emitting element in a plane direction, so as to illuminates the sample with illumination light through the tray in the housing; a lens that is disposed in the housing so as to face the plane light source with the tray interposed between the lens and the plane light source and is used for imaging the sample; and an imaging control unit that adjusts a focal length of the lens and performs imaging in a case of imaging the single sample.
  • the housing includes a sample loading door that is capable of being opened and closed, and a filter turret that has a plurality of filters for limiting a wavelength used for imaging by being inserted between the sample and the lens.
  • driving of the filter turret is stopped in a case where the sample loading door is opened.
  • the housing includes a sample loading door that is capable of being opened and closed, and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light.
  • the excitation light source is prevented from emitting light in a case where the sample loading door is opened.
  • the housing includes a sample loading door that is capable of being opened and closed.
  • the plane light source is prevented from emitting light in a case where the sample loading door is opened.
  • the imaging control unit adjusts the focal length of the lens and performs imaging, a plurality of times, in a case of imaging the single sample.
  • the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and a control unit that prevents the plane light source from emitting light in a case where the light blocking plate is inserted between the tray and the plane light source.
  • the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light.
  • a light blocking plate that is capable of being inserted and removed between the tray and the plane light source
  • a light blocking plate detection unit that detects insertion and removal of the light blocking plate
  • an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light.
  • the excitation light source is prevented from emitting light
  • the excitation light source is permitted to emit light.
  • the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light.
  • a warning is notified in a case where the light blocking plate is removed from between the tray and the plane light source and imaging of the sample using the fluorescent light is intended to be performed.
  • a live view mode in which the plane light source is turned off and a moving image of the sample placed on the tray is captured, is provided.
  • the housing includes a sample loading door that is capable of being opened and closed.
  • the live view mode is executed in a case where the sample loading door is opened.
  • the housing includes a sample loading door that is capable of being opened and closed.
  • the live view mode is executed until the sample loading door is closed.
  • the present invention it is possible to provide a sample imaging apparatus which suppresses heat generation of a light source so as to reduce the environmental change in the housing due to the heat generation of the light source.
  • FIG. 1 is an external view of a sample imaging apparatus.
  • FIG. 2 is an explanatory diagram illustrating an optical configuration of a sample imaging apparatus.
  • FIG. 3 is a block diagram of an imaging unit.
  • FIG. 4 is a graph illustrating longitudinal chromatic aberration of a lens used in a sample imaging apparatus.
  • FIG. 5 is a filter turret.
  • FIG. 6 is an explanatory diagram illustrating a configuration of a plane light source.
  • FIG. 7 is a block diagram illustrating an electrical configuration of a sample imaging apparatus.
  • FIG. 8 is a flowchart in a case of performing imaging by using a plurality of types of fluorescent light.
  • FIG. 9 is a flowchart in a case of performing imaging by using chemiluminescent light of a sample or the like.
  • a sample imaging apparatus 10 is an apparatus that images a sample 40 (refer to FIG. 2 ) such as biological molecules in a housing 11 forming a closed space.
  • the housing 11 has a substantially rectangular parallelepiped shape, and has a touch panel 12 on the upper front side.
  • the touch panel 12 is an operation unit and a display unit of the sample imaging apparatus 10 .
  • the touch panel 12 displays an operable menu for selecting an imaging menu and/or an image obtained by imaging the sample 40 .
  • a sample loading door 13 which is capable of being opened and closed in order to load a sample 40 as a subject, is provided on the lower part of the front surface of the housing 11 .
  • the housing 11 forms a closed space inside by closing the sample loading door 13 and the filter replacement window 14 .
  • the closed space is a space that forms a substantially constant imaging environment without being affected by the outside. Therefore, it is possible to provide a ventilating opening in the housing 11 for cooling or the like of a built-in device. It can be said that the housing 11 forms a closed space inside in a case where the inner space forms an imaging environment which is substantially not affected by the outside even in a case where air or the like enters and exits through the ventilating opening.
  • the sample imaging apparatus 10 comprises an imaging unit 21 that images the sample 40 , a first epi-illumination light source 22 , a second epi-illumination light source 23 , and a plane light source 24 , in the housing 11 .
  • the first epi-illumination light source 22 , the second epi-illumination light source 23 , and the plane light source 24 are arranged in this order from the imaging unit 21 present on the uppermost part in the housing 11 , along an imaging optical axis L 1 of the imaging unit 21 .
  • a tray 25 on which the sample 40 is placed in the housing 11 , is alternatively disposed at either of two positions, that is, a first position 31 or a second position 32 .
  • the first position 31 is between the first epi-illumination light source 22 and the second epi-illumination light source 23 .
  • the second position 32 is between the second epi-illumination light source 23 and the plane light source 24 .
  • the tray 25 is disposed at the first position 31 .
  • the tray 25 is made of, for example, glass and is transparent.
  • transparent of the tray 25 means that the illumination light emitted by the plane light source 24 is transmitted to such an extent that the imaging unit 21 is able to image the sample 40 using the tray 25 . Further, the term “transparent” includes guiding the illumination light by diffusing, scattering, or diffracting the illumination light emitted by the plane light source 24 toward the imaging unit 21 .
  • the first epi-illumination light source 22 irradiates the sample 40 with the illumination light from the side of the imaging unit 21 .
  • the illumination light emitted by the first epi-illumination light source 22 is, for example, excitation light that causes fluorescent light from the sample 40 or the fluorescent reagent added to the sample 40 by exciting the sample 40 or the fluorescent reagent added to the sample 40 .
  • the first epi-illumination light source 22 is able to emit excitation light that excites, for example, a Cy2 dye (cyanine dye), a Cy3 dye (indocarbocyanine dye), a Cy5 dye (indodicarbocyanine dye) or the like.
  • the Cy2 dye emits fluorescent light having a wavelength of about 510 nm by irradiating the dye with excitation light having a wavelength of about 492 nm.
  • the Cy3 dye emits fluorescent light having a wavelength of about 570 nm by irradiating the dye with excitation light having a wavelength of about 550 nm.
  • the Cy5 dye emits fluorescent light having a wavelength of about 670 nm by irradiating the dye with excitation light having a wavelength of about 650 nm.
  • the first epi-illumination light source 22 is able to emit ultraviolet light and infrared light.
  • the second epi-illumination light source 23 irradiates the sample 40 with the illumination light from the side of the imaging unit 21 .
  • the illumination light emitted by the second epi-illumination light source 23 is, for example, excitation light that causes fluorescent light from the sample 40 or the fluorescent reagent added to the sample 40 by exciting the sample 40 or the fluorescent reagent added to the sample 40 .
  • the illumination light (excitation light) which is capable of being emitted by the second epi-illumination light source 23 , is the same as that of the first epi-illumination light source 22 .
  • the first epi-illumination light source 22 and the second epi-illumination light source 23 each are an excitation light source which irradiates excitation light, which is for emitting fluorescent light, to the sample 40 placed on the tray 25 from the side of the lens 53 (refer to FIG. 3 ) included in the imaging unit 21 .
  • the plane light source 24 emits illumination light to the sample 40 through the tray 25 disposed at the first position 31 or the second position 32 in the housing 11 .
  • the plane light source 24 is used as a so-called transmission light source.
  • the illumination light emitted by the plane light source 24 has a substantially uniform amount of light over substantially the entire portion (flat surface) of the tray 25 on which the sample 40 is placed.
  • the plane light source 24 is able to emit red light, green light, blue light, or light (for example, white light) obtained by mixing two or more of them.
  • a black insert (hereinafter referred to as a light blocking plate) 28 is capable of being freely inserted and removed between the tray 25 at the second position 32 and the plane light source 24 .
  • the imaging unit 21 includes an imaging element 51 , a shutter 52 , a lens 53 , a filter turret 54 , and an imaging control unit 55 .
  • the imaging element 51 is, for example, a charge coupled device (CCD) sensor.
  • the shutter 52 is a so-called mechanical shutter.
  • the imaging element 51 and the lens 53 are disposed in the housing 11 so as to face the plane light source 24 with the tray 25 interposed therebetween.
  • the imaging element 51 , the lens 53 , and the filter turret 54 are used for imaging the sample 40 .
  • the lens 53 is a lens in which longitudinal chromatic aberration in a wavelength range of chemiluminescent light (chemiluminescence) emitted by the sample 40 or a chemiluminescent reagent added to the sample 40 is corrected. More specifically, the lens 53 is a so-called achromatic lens, and as illustrated in FIG. 4 , the longitudinal chromatic aberration of the lens 53 has a bell-shaped residual error. However, the general achromatic lens (comparative example) is adjusted such that the focus shift becomes zero at the F line and the C line. In contrast, the lens 53 used in the sample imaging apparatus 10 is characterized in that the focus shift becomes substantially infinitesimal and minimal in the wavelength range of the chemiluminescent light of the sample 40 or the like.
  • the focus shift of the lens 53 is greater as the wavelength is longer. Furthermore, an amount of focus shift ⁇ CL in the wavelength range of the chemiluminescent light is less than an amount of focus shift ⁇ FL in the wavelength range of the fluorescent light.
  • the “wavelength range of the chemiluminescent light” is an emission band of the sample 40 or the chemiluminescent reagent (such as luminol) usually added to the sample 40 , and refers to, for example, a wavelength range of about 350 nm to about 480 nm.
  • the “wavelength range of the fluorescent light” refers to a wavelength range of the fluorescent light emitted by the sample 40 or a fluorescent reagent (such as Cy3 dye) generally added to the sample 40 , for example, a wavelength of about 500 nm to about 700 nm.
  • the filter turret 54 comprises a plurality of optical filters 61 to 68 disposed between the lens 53 and the sample 40 . Then, by rotating the filter turret 54 , any one of these optical filters 61 to 68 is capable of being selected and appropriately inserted on the imaging optical axis L 1 .
  • the optical filters 61 to 68 include a plurality of optical filters for limiting the wavelength used for imaging.
  • the sample imaging apparatus 10 automatically rotates the filter turret 54 in accordance with the imaging menu. Thereby, the sample imaging apparatus 10 automatically selects an optical filter appropriate for imaging among the optical filters 61 to 68 appropriate for imaging.
  • the optical filter 61 is a so-called “pass-through” and transmits light with substantially the entire wavelength range.
  • the optical filter 61 is defined to include a case where the optical filter is not actually provided.
  • the optical filter 62 is, for example, an infrared (IR) long pass filter
  • the optical filter 63 is, for example, an IR short pass filter.
  • the optical filter 64 is, for example, a band pass filter for Cy5 dye
  • the optical filter 65 is, for example, a band pass filter for Cy3 dye and ultraviolet light
  • the optical filter 66 is a band pass filter for Cy2 dye.
  • the optical filter 67 and the optical filter 68 are custom filters optionally set by the user.
  • Each of the optical filters 62 to 68 other than the optical filter 61 which is a pass-through is a filter unit 71 which is detachable from the filter turret 54 , and all of them are replaceable. Since each filter unit 71 has an identifier 72 attached thereto, the sample imaging apparatus 10 is able to use the identifier 72 to identify what kind of optical filter is attached to which position on the filter turret 54 .
  • the optical filters 62 to 66 other than the optical filter 67 and the optical filter 68 which are custom filters are arranged from the vicinity of the optical filter 61 which is a pass-through, in the order of longer wavelengths (or in the order of shorter wavelengths). The reason for this is that the arrangement has to match with the imaging sequence for shortening the imaging time period.
  • the imaging control unit 55 controls each unit of the imaging unit 21 .
  • the imaging control unit 55 adjusts the focal length of the lens 53 in accordance with the imaging menu.
  • the imaging control unit 55 also performs the operation of the imaging element 51 , the opening and closing of the shutter 52 , the rotation of the filter turret 54 (selection of the optical filter), and the like in accordance with the imaging menu.
  • the plane light source 24 is formed by using a light emitting unit 82 including one or more light emitting elements 81 , and a light guide plate 83 having a flat plate shape that propagates the light emitted by the light emitting elements 81 in a plane direction (in an XY in-plane direction in FIG. 6 ).
  • the light emitting element 81 is, for example, a light emitting diode (LED).
  • the light guide plate 83 is connected to the light emitting unit 82 on the side surface. Therefore, the light emitted from the light emitting element 81 is incident into the light guide plate 83 from the side surface of the light guide plate 83 .
  • a light amount adjustment pattern 85 is provided on the surface 83 b of the light guide plate 83 such that the amount of light emitted from the light guide plate 83 increases as the distance from the light emitting element 81 increases.
  • the light amount adjustment pattern 85 is formed of a plurality of reflectors that reflect light propagating in the light guide plate 83 , and the area of each reflector increases as the distance from the light emitting element 81 increases.
  • a diffusion film or a diffusion plate (not shown) is capable of being provided on the surface 83 a facing the surface 83 b (the surface facing the imaging unit 21 (lens 53 ) side) as needed.
  • the light amount adjustment pattern 85 is formed of a reflector, but the light amount adjustment pattern 85 may be formed of a light blocker having a plurality of light transmitting portions (openings and the like). It is preferable that the light amount adjustment pattern formed by the light blocker is provided on the surface 83 a of the light guide plate 83 , and a reflective film or a reflector is provided on the surface 83 b.
  • the plane light source 24 configured as described above has a high light guiding efficiency. Therefore, it is possible to reduce the number of light emitting elements 81 . As a result, the heat generation of the plane light source 24 is suppressed. In addition, it is possible to reduce the environmental change in the housing 11 constituting the closed space.
  • the sample imaging apparatus 10 comprises a control unit 91 , a door open/close detection unit 92 , a tray detection unit 93 , and a light blocking plate detection unit 94 .
  • the control unit 91 integrally controls each part of the sample imaging apparatus 10 .
  • the first epi-illumination light source 22 , the second epi-illumination light source 23 , and the plane light source 24 are turned on or off.
  • the control unit 91 controls each unit of the imaging unit 21 through the imaging control unit 55 , and performs imaging of the sample 40 in an appropriate imaging sequence in accordance with the imaging menu.
  • the door open/close detection unit 92 detects open/close states of the sample loading door 13 and the filter replacement window 14 .
  • the tray detection unit 93 detects the tray 25 .
  • the detection of the tray 25 is detection of whether or not the tray 25 is disposed in the housing 11 and detection of which of the first position 31 and the second position 32 the tray 25 is disposed.
  • the light blocking plate detection unit 94 detects that the light blocking plate 28 is inserted.
  • the detection of the light blocking plate 28 is detection as to whether or not the light blocking plate 28 is inserted on the imaging optical axis L 1 .
  • the control unit 91 controls the operation of the sample imaging apparatus 10 by using the detection results of these detection units.
  • the sample imaging apparatus 10 adjusts the focal length of the lens 53 for each imaging. That is, in a case of imaging one sample 40 , the imaging control unit 55 adjusts the focal length of the lens 53 a plurality of times, thereby performing imaging. Further, a state of focusing on a long wavelength side changed from a state of focusing on a short wavelength side is compared with the state of focusing on the short wavelength side changed from the state of focusing on the long wavelength side.
  • imaging is performed sequentially from imaging using the light with a short wavelength.
  • the imaging using the fluorescent light of the Cy2 dye and the imaging using the fluorescent light of the Cy3 dye may be performed.
  • imaging is performed by performing focusing for imaging using the fluorescent light of Cy2 dye that emits fluorescent light with a shorter wavelength, and then imaging is performed by performing focusing for imaging using the fluorescent light of Cy3 dye that emits fluorescent light with a relatively longer wavelength.
  • a state of focusing on a long wavelength side changed from a state of focusing on a short wavelength side is compared with the state of focusing on the short wavelength side changed from the state of focusing on the long wavelength side.
  • the sample imaging apparatus 10 performs imaging sequentially from imaging using the fluorescent light with a long wavelength.
  • the sample imaging apparatus 10 adjusts the focal length of the lens 53 for each imaging in a case of imaging one sample 40 a plurality of times.
  • the sample imaging apparatus 10 adjusts the focal length of the lens 53 also in a case of imaging one sample 40 once.
  • the sample imaging apparatus 10 uses the lens 53 capable of adjusting the focal length.
  • the sample imaging apparatus 10 is able to image the sample 40 by using a single focus lens instead of the lens 53 .
  • the imaging control unit 55 performs imaging by focusing on the sample 40 through the single focus lens.
  • the sample imaging apparatus 10 first performs imaging using the chemiluminescent light.
  • the reason for this is that the chemiluminescent light becomes weak as time passes.
  • imaging using the fluorescent light is performed.
  • the reason for this is that it is possible to adjust the emission intensity of the fluorescent light by performing adjustment of the irradiation intensity of the excitation light or the like.
  • the imaging using the fluorescent light is performed in the order of reducing the error of the focal length due to backlash as described above.
  • the images obtained through the respective imaging operations are capable of being sequentially displayed on the touch panel 12 .
  • the images obtained through the respective imaging operations may be arranged and displayed on the touch panel 12 .
  • control unit 91 is able to prevent the plane light source 24 from emitting light.
  • the control unit 91 prevents the first epi-illumination light source 22 and the second epi-illumination light source 23 from emitting light.
  • the light blocking plate 28 is inserted between the tray 25 and the plane light source 24 , it is possible to permit the first epi-illumination light source 22 and the second epi-illumination light source 23 to emit light. The reason for this is to appropriately perform imaging using the first epi-illumination light source 22 and the second epi-illumination light source 23 .
  • the control unit 91 is able to issue notification of a warning in a case of removing the light blocking plate 28 from between the tray 25 and the plane light source 24 and attempting to perform imaging of the sample 40 using the fluorescent light.
  • warning is defined to include display of a message on the touch panel 12 and the like.
  • the sample imaging apparatus 10 has a live view mode in which the plane light source 24 is turned off and a moving image of the sample 40 placed on the tray 25 is captured.
  • the moving image in the live view mode is displayed on the touch panel 12 .
  • the control unit 91 executes the live view mode.
  • the control unit 91 is able to execute the live view mode until the sample loading door 13 is closed.
  • the control unit 91 stops the drive (rotation operation or the like) of the filter turret 54 , in a case where the sample loading door 13 is opened. This is for safety since the user is likely to touch the filter turret 54 .
  • the control unit 91 is able to prevent the first epi-illumination light source 22 and the second epi-illumination light source 23 , which are excitation light sources, from emitting light in a case where the sample loading door 13 is opened. Similarly, the control unit 91 is able to prevent the plane light source 24 from emitting light in a case where the sample loading door 13 is opened. Each of these light sources has high brightness and is therefore safe.
  • the hardware structure of the processing unit which executes various kinds of processing of the imaging control unit 55 , the control unit 91 , and the like, is various processors as described below.
  • the various processors include: a central processing unit (CPU) and a graphic processing unit (GPU) that are general purpose processors which execute software (programs) and function as various processing units; a programmable logic device (PLD) that is a processor capable of changing a circuit configuration after manufacture of a field programmable gate array (FPGA) or the like; and a dedicated electric circuit that is a processor having a circuit configuration specially designed to execute various processes.
  • CPU central processing unit
  • GPU graphic processing unit
  • PLD programmable logic device
  • FPGA field programmable gate array
  • One processing unit may be configured as one of these various types of processors, or may be configured as a combination of two or more processors of the same or different types (such as a plurality of FPGAs, a combination of a CPU and an FPGA, or a combination of a CPU and a GPU). Further, a plurality of processing units may be configured as one processor.
  • one processor is configured as a combination of one or more CPUs and software as typified by computers such as clients and servers, and this processor functions as a plurality of processing units.
  • SoC system on chip
  • the various processing units are configured using one or more of the above-mentioned various processors as a hardware structure.
  • the hardware structures of these various processors each are, more specifically, an electrical circuit (circuitry) having a configuration in which circuit elements such as semiconductor elements are combined.

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  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

The sample imaging apparatus includes: a housing that forms a closed space; a transparent tray on which a sample is placed in the housing; a plane light source that is formed by using a flat light guide plate, which propagates light emitted by a light emitting element in a plane direction, so as to illuminates the sample with illumination light through the tray in the housing; a lens that is disposed in the housing so as to face the plane light source with the tray interposed between the lens and the plane light source and is used for imaging the sample; and an imaging control unit that adjusts a focal length of the lens and performs imaging in a case of imaging the single sample.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C § 119(a) to Japanese Patent Application No. 2018-183005 filed on Sep. 27, 2018. The above application is hereby expressly incorporated by reference, in its entirety, into the present application.
BACKGROUND OF THE INVENTION 1. Field of the Invention
The present invention relates to a sample imaging apparatus that irradiates a sample with light in a closed space to capture an image.
2. Description of the Related Art
There is a known imaging apparatus that images a sample by using transmitted light in order to analyze a sample such as biological molecules (JP2015-177250A, corresponding to U.S. Pat. No. 9,531,950B2). In this imaging apparatus, the sample which is a subject, a lens, a light source, and the like are arranged in a housing, whereby the sample is imaged. Further, a plane light source, in which a light guide using a reflective diffusion plate and a transmission diffusion plate is formed, is used.
SUMMARY OF THE INVENTION
A sample imaging apparatus, which images a sample such as biological molecules usually, performs imaging by arranging not only a sample as a subject but also a lens, a light source, and the like in a housing forming a closed space. Moreover, in order to appropriately perform analysis and the like, samples such as biological molecules have to be imaged on a certain environmental condition.
However, in a case where the heat generation of the light source used for imaging is large, the temperature in the housing may rise and the state of the sample may change. In addition, in a case where the type of light to be emitted to the sample is changed and imaging is performed a plurality of times, it takes a long time to complete the imaging. In such a case, the effect of the temperature change in the housing due to the heat generation of the light source is serious.
Therefore, it is an object of the present invention to provide a sample imaging apparatus which suppresses heat generation of a light source so as to reduce the environmental change in the housing due to the heat generation of the light source.
According to the present invention, there is provided a sample imaging apparatus comprising: a housing that forms a closed space; a transparent tray on which a sample is placed in the housing; a plane light source that is formed by using a flat light guide plate, which propagates light emitted by a light emitting element in a plane direction, so as to illuminates the sample with illumination light through the tray in the housing; a lens that is disposed in the housing so as to face the plane light source with the tray interposed between the lens and the plane light source and is used for imaging the sample; and an imaging control unit that adjusts a focal length of the lens and performs imaging in a case of imaging the single sample.
It is preferable that the housing includes a sample loading door that is capable of being opened and closed, and a filter turret that has a plurality of filters for limiting a wavelength used for imaging by being inserted between the sample and the lens. In addition, it is preferable that driving of the filter turret is stopped in a case where the sample loading door is opened.
It is preferable that the housing includes a sample loading door that is capable of being opened and closed, and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light. In addition, it is preferable that the excitation light source is prevented from emitting light in a case where the sample loading door is opened.
It is preferable that the housing includes a sample loading door that is capable of being opened and closed. In addition, it is preferable that the plane light source is prevented from emitting light in a case where the sample loading door is opened.
It is preferable that the imaging control unit adjusts the focal length of the lens and performs imaging, a plurality of times, in a case of imaging the single sample.
It is preferable that the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and a control unit that prevents the plane light source from emitting light in a case where the light blocking plate is inserted between the tray and the plane light source.
It is preferable that the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light. In addition, it is preferable that in a case where the light blocking plate is removed from between the tray and the plane light source, the excitation light source is prevented from emitting light, and in a case where the light blocking plate is inserted between the tray and the plane light source, the excitation light source is permitted to emit light.
It is preferable that the sample imaging apparatus further comprises: a light blocking plate that is capable of being inserted and removed between the tray and the plane light source; a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light. In addition, it is preferable that in a case where the light blocking plate is removed from between the tray and the plane light source and imaging of the sample using the fluorescent light is intended to be performed, a warning is notified.
It is preferable that a live view mode, in which the plane light source is turned off and a moving image of the sample placed on the tray is captured, is provided.
It is preferable that the housing includes a sample loading door that is capable of being opened and closed. In addition, it is preferable that the live view mode is executed in a case where the sample loading door is opened.
It is preferable that the housing includes a sample loading door that is capable of being opened and closed. In addition, it is preferable that in a case where the sample loading door is opened and the tray is set, the live view mode is executed until the sample loading door is closed.
According to the present invention, it is possible to provide a sample imaging apparatus which suppresses heat generation of a light source so as to reduce the environmental change in the housing due to the heat generation of the light source.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an external view of a sample imaging apparatus.
FIG. 2 is an explanatory diagram illustrating an optical configuration of a sample imaging apparatus.
FIG. 3 is a block diagram of an imaging unit.
FIG. 4 is a graph illustrating longitudinal chromatic aberration of a lens used in a sample imaging apparatus.
FIG. 5 is a filter turret.
FIG. 6 is an explanatory diagram illustrating a configuration of a plane light source.
FIG. 7 is a block diagram illustrating an electrical configuration of a sample imaging apparatus.
FIG. 8 is a flowchart in a case of performing imaging by using a plurality of types of fluorescent light.
FIG. 9 is a flowchart in a case of performing imaging by using chemiluminescent light of a sample or the like.
 DESCRIPTION OF THE PREFERRED EMBODIMENTS
As illustrated in FIG. 1, a sample imaging apparatus 10 is an apparatus that images a sample 40 (refer to FIG. 2) such as biological molecules in a housing 11 forming a closed space. The housing 11 has a substantially rectangular parallelepiped shape, and has a touch panel 12 on the upper front side. The touch panel 12 is an operation unit and a display unit of the sample imaging apparatus 10. The touch panel 12 displays an operable menu for selecting an imaging menu and/or an image obtained by imaging the sample 40. Further, a sample loading door 13, which is capable of being opened and closed in order to load a sample 40 as a subject, is provided on the lower part of the front surface of the housing 11. In addition, on the side surface of the housing 11, there is a filter replacement window 14 for replacing a filter or the like used for imaging.
The housing 11 forms a closed space inside by closing the sample loading door 13 and the filter replacement window 14. The closed space is a space that forms a substantially constant imaging environment without being affected by the outside. Therefore, it is possible to provide a ventilating opening in the housing 11 for cooling or the like of a built-in device. It can be said that the housing 11 forms a closed space inside in a case where the inner space forms an imaging environment which is substantially not affected by the outside even in a case where air or the like enters and exits through the ventilating opening.
As illustrated in FIG. 2, the sample imaging apparatus 10 comprises an imaging unit 21 that images the sample 40, a first epi-illumination light source 22, a second epi-illumination light source 23, and a plane light source 24, in the housing 11. The first epi-illumination light source 22, the second epi-illumination light source 23, and the plane light source 24 are arranged in this order from the imaging unit 21 present on the uppermost part in the housing 11, along an imaging optical axis L1 of the imaging unit 21.
A tray 25, on which the sample 40 is placed in the housing 11, is alternatively disposed at either of two positions, that is, a first position 31 or a second position 32. The first position 31 is between the first epi-illumination light source 22 and the second epi-illumination light source 23. The second position 32 is between the second epi-illumination light source 23 and the plane light source 24. In FIG. 2, the tray 25 is disposed at the first position 31. The tray 25 is made of, for example, glass and is transparent. The term “transparent” of the tray 25 means that the illumination light emitted by the plane light source 24 is transmitted to such an extent that the imaging unit 21 is able to image the sample 40 using the tray 25. Further, the term “transparent” includes guiding the illumination light by diffusing, scattering, or diffracting the illumination light emitted by the plane light source 24 toward the imaging unit 21.
In a case where the tray 25 on which the sample 40 is placed is disposed at the first position 31, the first epi-illumination light source 22 irradiates the sample 40 with the illumination light from the side of the imaging unit 21. The illumination light emitted by the first epi-illumination light source 22 is, for example, excitation light that causes fluorescent light from the sample 40 or the fluorescent reagent added to the sample 40 by exciting the sample 40 or the fluorescent reagent added to the sample 40. The first epi-illumination light source 22 is able to emit excitation light that excites, for example, a Cy2 dye (cyanine dye), a Cy3 dye (indocarbocyanine dye), a Cy5 dye (indodicarbocyanine dye) or the like. The Cy2 dye emits fluorescent light having a wavelength of about 510 nm by irradiating the dye with excitation light having a wavelength of about 492 nm. The Cy3 dye emits fluorescent light having a wavelength of about 570 nm by irradiating the dye with excitation light having a wavelength of about 550 nm. The Cy5 dye emits fluorescent light having a wavelength of about 670 nm by irradiating the dye with excitation light having a wavelength of about 650 nm. Besides, the first epi-illumination light source 22 is able to emit ultraviolet light and infrared light.
In a case where the tray 25 on which the sample 40 is placed is disposed at the second position 32, the second epi-illumination light source 23 irradiates the sample 40 with the illumination light from the side of the imaging unit 21. Further, the illumination light emitted by the second epi-illumination light source 23 is, for example, excitation light that causes fluorescent light from the sample 40 or the fluorescent reagent added to the sample 40 by exciting the sample 40 or the fluorescent reagent added to the sample 40. The illumination light (excitation light), which is capable of being emitted by the second epi-illumination light source 23, is the same as that of the first epi-illumination light source 22. That is, the first epi-illumination light source 22 and the second epi-illumination light source 23 each are an excitation light source which irradiates excitation light, which is for emitting fluorescent light, to the sample 40 placed on the tray 25 from the side of the lens 53 (refer to FIG. 3) included in the imaging unit 21.
The plane light source 24 emits illumination light to the sample 40 through the tray 25 disposed at the first position 31 or the second position 32 in the housing 11. In the sample imaging apparatus 10, the plane light source 24 is used as a so-called transmission light source. Further, the illumination light emitted by the plane light source 24 has a substantially uniform amount of light over substantially the entire portion (flat surface) of the tray 25 on which the sample 40 is placed. The plane light source 24 is able to emit red light, green light, blue light, or light (for example, white light) obtained by mixing two or more of them.
In addition to the above-mentioned description, a black insert (hereinafter referred to as a light blocking plate) 28 is capable of being freely inserted and removed between the tray 25 at the second position 32 and the plane light source 24.
As illustrated in FIG. 3, the imaging unit 21 includes an imaging element 51, a shutter 52, a lens 53, a filter turret 54, and an imaging control unit 55. The imaging element 51 is, for example, a charge coupled device (CCD) sensor. The shutter 52 is a so-called mechanical shutter.
The imaging element 51 and the lens 53 are disposed in the housing 11 so as to face the plane light source 24 with the tray 25 interposed therebetween. The imaging element 51, the lens 53, and the filter turret 54 are used for imaging the sample 40.
The lens 53 is a lens in which longitudinal chromatic aberration in a wavelength range of chemiluminescent light (chemiluminescence) emitted by the sample 40 or a chemiluminescent reagent added to the sample 40 is corrected. More specifically, the lens 53 is a so-called achromatic lens, and as illustrated in FIG. 4, the longitudinal chromatic aberration of the lens 53 has a bell-shaped residual error. However, the general achromatic lens (comparative example) is adjusted such that the focus shift becomes zero at the F line and the C line. In contrast, the lens 53 used in the sample imaging apparatus 10 is characterized in that the focus shift becomes substantially infinitesimal and minimal in the wavelength range of the chemiluminescent light of the sample 40 or the like. Further, in the range of visible light, the focus shift of the lens 53 is greater as the wavelength is longer. Furthermore, an amount of focus shift ΔCL in the wavelength range of the chemiluminescent light is less than an amount of focus shift ΔFL in the wavelength range of the fluorescent light. In the present specification, the “wavelength range of the chemiluminescent light” is an emission band of the sample 40 or the chemiluminescent reagent (such as luminol) usually added to the sample 40, and refers to, for example, a wavelength range of about 350 nm to about 480 nm. In addition, in the present specification, the “wavelength range of the fluorescent light” refers to a wavelength range of the fluorescent light emitted by the sample 40 or a fluorescent reagent (such as Cy3 dye) generally added to the sample 40, for example, a wavelength of about 500 nm to about 700 nm.
As illustrated in FIG. 5, the filter turret 54 comprises a plurality of optical filters 61 to 68 disposed between the lens 53 and the sample 40. Then, by rotating the filter turret 54, any one of these optical filters 61 to 68 is capable of being selected and appropriately inserted on the imaging optical axis L1. The optical filters 61 to 68 include a plurality of optical filters for limiting the wavelength used for imaging. The sample imaging apparatus 10 automatically rotates the filter turret 54 in accordance with the imaging menu. Thereby, the sample imaging apparatus 10 automatically selects an optical filter appropriate for imaging among the optical filters 61 to 68 appropriate for imaging.
The optical filter 61 is a so-called “pass-through” and transmits light with substantially the entire wavelength range. For convenience of description, the optical filter 61 is defined to include a case where the optical filter is not actually provided. The optical filter 62 is, for example, an infrared (IR) long pass filter, and the optical filter 63 is, for example, an IR short pass filter. The optical filter 64 is, for example, a band pass filter for Cy5 dye, the optical filter 65 is, for example, a band pass filter for Cy3 dye and ultraviolet light, and the optical filter 66 is a band pass filter for Cy2 dye. The optical filter 67 and the optical filter 68 are custom filters optionally set by the user. Each of the optical filters 62 to 68 other than the optical filter 61 which is a pass-through is a filter unit 71 which is detachable from the filter turret 54, and all of them are replaceable. Since each filter unit 71 has an identifier 72 attached thereto, the sample imaging apparatus 10 is able to use the identifier 72 to identify what kind of optical filter is attached to which position on the filter turret 54.
In the filter turret 54, the optical filters 62 to 66 other than the optical filter 67 and the optical filter 68 which are custom filters are arranged from the vicinity of the optical filter 61 which is a pass-through, in the order of longer wavelengths (or in the order of shorter wavelengths). The reason for this is that the arrangement has to match with the imaging sequence for shortening the imaging time period.
The imaging control unit 55 controls each unit of the imaging unit 21. For example, the imaging control unit 55 adjusts the focal length of the lens 53 in accordance with the imaging menu. The imaging control unit 55 also performs the operation of the imaging element 51, the opening and closing of the shutter 52, the rotation of the filter turret 54 (selection of the optical filter), and the like in accordance with the imaging menu.
As illustrated in FIG. 6, the plane light source 24 is formed by using a light emitting unit 82 including one or more light emitting elements 81, and a light guide plate 83 having a flat plate shape that propagates the light emitted by the light emitting elements 81 in a plane direction (in an XY in-plane direction in FIG. 6). The light emitting element 81 is, for example, a light emitting diode (LED). The light guide plate 83 is connected to the light emitting unit 82 on the side surface. Therefore, the light emitted from the light emitting element 81 is incident into the light guide plate 83 from the side surface of the light guide plate 83. A light amount adjustment pattern 85 is provided on the surface 83 b of the light guide plate 83 such that the amount of light emitted from the light guide plate 83 increases as the distance from the light emitting element 81 increases. The light amount adjustment pattern 85 is formed of a plurality of reflectors that reflect light propagating in the light guide plate 83, and the area of each reflector increases as the distance from the light emitting element 81 increases. On the other hand, for example, a diffusion film or a diffusion plate (not shown) is capable of being provided on the surface 83 a facing the surface 83 b (the surface facing the imaging unit 21 (lens 53) side) as needed. In the present embodiment, the light amount adjustment pattern 85 is formed of a reflector, but the light amount adjustment pattern 85 may be formed of a light blocker having a plurality of light transmitting portions (openings and the like). It is preferable that the light amount adjustment pattern formed by the light blocker is provided on the surface 83 a of the light guide plate 83, and a reflective film or a reflector is provided on the surface 83 b.
As compared with the plane light source constituted by using a reflection plate and a diffusion plate, the plane light source 24 configured as described above has a high light guiding efficiency. Therefore, it is possible to reduce the number of light emitting elements 81. As a result, the heat generation of the plane light source 24 is suppressed. In addition, it is possible to reduce the environmental change in the housing 11 constituting the closed space.
In addition to the above, as illustrated in FIG. 7, the sample imaging apparatus 10 comprises a control unit 91, a door open/close detection unit 92, a tray detection unit 93, and a light blocking plate detection unit 94.
The control unit 91 integrally controls each part of the sample imaging apparatus 10. For example, the first epi-illumination light source 22, the second epi-illumination light source 23, and the plane light source 24 are turned on or off. Further, the control unit 91 controls each unit of the imaging unit 21 through the imaging control unit 55, and performs imaging of the sample 40 in an appropriate imaging sequence in accordance with the imaging menu.
The door open/close detection unit 92 detects open/close states of the sample loading door 13 and the filter replacement window 14. The tray detection unit 93 detects the tray 25. The detection of the tray 25 is detection of whether or not the tray 25 is disposed in the housing 11 and detection of which of the first position 31 and the second position 32 the tray 25 is disposed. The light blocking plate detection unit 94 detects that the light blocking plate 28 is inserted. The detection of the light blocking plate 28 is detection as to whether or not the light blocking plate 28 is inserted on the imaging optical axis L1. The control unit 91 controls the operation of the sample imaging apparatus 10 by using the detection results of these detection units.
Hereinafter, an operation sequence of the sample imaging apparatus 10 configured as described above will be described. First, in a case of imaging the sample 40 by using a plurality of types of fluorescent light, the sample imaging apparatus 10 adjusts the focal length of the lens 53 for each imaging. That is, in a case of imaging one sample 40, the imaging control unit 55 adjusts the focal length of the lens 53 a plurality of times, thereby performing imaging. Further, a state of focusing on a long wavelength side changed from a state of focusing on a short wavelength side is compared with the state of focusing on the short wavelength side changed from the state of focusing on the long wavelength side. In a case where an error of the focal length is smaller in the state of focusing on the long wavelength side changed from the state of focusing on the short wavelength side, imaging is performed sequentially from imaging using the light with a short wavelength. For example, as illustrated in FIG. 8, the imaging using the fluorescent light of the Cy2 dye and the imaging using the fluorescent light of the Cy3 dye may be performed. In this case, imaging is performed by performing focusing for imaging using the fluorescent light of Cy2 dye that emits fluorescent light with a shorter wavelength, and then imaging is performed by performing focusing for imaging using the fluorescent light of Cy3 dye that emits fluorescent light with a relatively longer wavelength.
A state of focusing on a long wavelength side changed from a state of focusing on a short wavelength side is compared with the state of focusing on the short wavelength side changed from the state of focusing on the long wavelength side. In a case where an error of the focal length is smaller in the state of focusing on the short wavelength side changed from the state of focusing on the long wavelength side, the sample imaging apparatus 10 performs imaging sequentially from imaging using the fluorescent light with a long wavelength.
As described above, by performing focusing for each imaging, it is possible to obtain an image with high image quality that is in focus in each imaging. Then, in a case of performing a plurality of imaging operations, by sequentially performing imaging from imaging using light of a relatively shorter wavelength (or longer wavelength), it is possible to obtain the image with high image quality that is in focus in each imaging operation even in a case where the plurality of imaging operations are sequentially performed. The reason for this is that it is possible to reduce backlash of a gear or the like for driving the lens 53. It is the same for the housing where three types of imaging are sequentially performed.
In addition, in the above-mentioned embodiment, the sample imaging apparatus 10 adjusts the focal length of the lens 53 for each imaging in a case of imaging one sample 40 a plurality of times. However, as a matter of course, the sample imaging apparatus 10 adjusts the focal length of the lens 53 also in a case of imaging one sample 40 once.
In the above-mentioned embodiment, the sample imaging apparatus 10 uses the lens 53 capable of adjusting the focal length. However, the sample imaging apparatus 10 is able to image the sample 40 by using a single focus lens instead of the lens 53. In such a case, in a case of imaging one sample 40, the imaging control unit 55 performs imaging by focusing on the sample 40 through the single focus lens.
In a case of performing imaging using chemiluminescent light of the sample 40 or the like is performed, for example, as illustrated in FIG. 9, the sample imaging apparatus 10 first performs imaging using the chemiluminescent light. The reason for this is that the chemiluminescent light becomes weak as time passes. Thereafter, imaging using the fluorescent light is performed. The reason for this is that it is possible to adjust the emission intensity of the fluorescent light by performing adjustment of the irradiation intensity of the excitation light or the like. The imaging using the fluorescent light is performed in the order of reducing the error of the focal length due to backlash as described above.
In a case where a plurality of imaging operations are performed, the images obtained through the respective imaging operations are capable of being sequentially displayed on the touch panel 12. In a case where a part or all of the imaging operations is completed, the images obtained through the respective imaging operations may be arranged and displayed on the touch panel 12. Further, in the case of performing the plurality of imaging operations, it is also possible to display, on the touch panel 12, a composite image obtained by combining a part or all of the images obtained through the respective imaging operations.
In a case where the light blocking plate 28 is inserted between the tray 25 and the plane light source 24, the control unit 91 is able to prevent the plane light source 24 from emitting light.
In a case where the light blocking plate 28 is removed from between the tray 25 and the plane light source 24, the control unit 91 prevents the first epi-illumination light source 22 and the second epi-illumination light source 23 from emitting light. In a case where the light blocking plate 28 is inserted between the tray 25 and the plane light source 24, it is possible to permit the first epi-illumination light source 22 and the second epi-illumination light source 23 to emit light. The reason for this is to appropriately perform imaging using the first epi-illumination light source 22 and the second epi-illumination light source 23.
The control unit 91 is able to issue notification of a warning in a case of removing the light blocking plate 28 from between the tray 25 and the plane light source 24 and attempting to perform imaging of the sample 40 using the fluorescent light. The term “warning” is defined to include display of a message on the touch panel 12 and the like.
The sample imaging apparatus 10 has a live view mode in which the plane light source 24 is turned off and a moving image of the sample 40 placed on the tray 25 is captured. The moving image in the live view mode is displayed on the touch panel 12. Further, for example, in a case where the sample loading door 13 is opened, the control unit 91 executes the live view mode. In addition, in a case where the sample loading door 13 is opened and the tray 25 is set, the control unit 91 is able to execute the live view mode until the sample loading door 13 is closed.
The control unit 91 stops the drive (rotation operation or the like) of the filter turret 54, in a case where the sample loading door 13 is opened. This is for safety since the user is likely to touch the filter turret 54.
The control unit 91 is able to prevent the first epi-illumination light source 22 and the second epi-illumination light source 23, which are excitation light sources, from emitting light in a case where the sample loading door 13 is opened. Similarly, the control unit 91 is able to prevent the plane light source 24 from emitting light in a case where the sample loading door 13 is opened. Each of these light sources has high brightness and is therefore safe.
In the above-mentioned embodiment, the hardware structure of the processing unit, which executes various kinds of processing of the imaging control unit 55, the control unit 91, and the like, is various processors as described below. The various processors include: a central processing unit (CPU) and a graphic processing unit (GPU) that are general purpose processors which execute software (programs) and function as various processing units; a programmable logic device (PLD) that is a processor capable of changing a circuit configuration after manufacture of a field programmable gate array (FPGA) or the like; and a dedicated electric circuit that is a processor having a circuit configuration specially designed to execute various processes.
One processing unit may be configured as one of these various types of processors, or may be configured as a combination of two or more processors of the same or different types (such as a plurality of FPGAs, a combination of a CPU and an FPGA, or a combination of a CPU and a GPU). Further, a plurality of processing units may be configured as one processor.
As an example in which a plurality of processing units are configured as one processor, there is a following configuration. First, one processor is configured as a combination of one or more CPUs and software as typified by computers such as clients and servers, and this processor functions as a plurality of processing units. Second, as typified by a system on chip (SoC) or the like, there is a configuration using a processor in which the function of the whole system including the plurality of processing units is implemented by one integrated circuit (IC) chip. In such a manner, the various processing units are configured using one or more of the above-mentioned various processors as a hardware structure.
The hardware structures of these various processors each are, more specifically, an electrical circuit (circuitry) having a configuration in which circuit elements such as semiconductor elements are combined.
EXPLANATION OF REFERENCES
    • 10 sample imaging apparatus
    • 11 housing
    • 12 touch panel
    • 13 sample loading door
    • 14 filter replacement window
    • 21 imaging unit
    • 22 first epi-illumination light source
    • 23 second epi-illumination light source
    • 24 area light source
    • 25 tray
    • 28 light blocking plate
    • 31 first position
    • 32 second position
    • 40 sample
    • 51 imaging element
    • 52 shutter
    • 53 lens
    • 54 filter turret
    • 55 imaging control unit
    • 61-68 optical filter
    • 71 filter unit
    • 72 identifier
    • 81 light emitting element
    • 82 light emitting unit
    • 83 light guide plate
    • 83 a, 83 b surface
    • 85 light adjustment pattern
    • 91 control unit
    • 92 door open/close detection unit
    • 93 tray detection unit
    • 94 light blocking plate detection unit
    • L1 imaging optical axis

Claims (8)

What is claimed is:
1. A sample imaging apparatus comprising:
a housing that forms a closed space;
a transparent tray on which a sample is placed in the housing;
a plane light source that is formed by using a flat light guide plate, which propagates light emitted by a light emitting element in a plane direction, so as to illuminates the sample with illumination light through the tray in the housing;
a lens that is disposed in the housing so as to face the plane light source with the tray interposed between the lens and the plane light source and is used for imaging the sample; and
an imaging control unit that adjusts a focal length of the lens and performs imaging in a case of imaging the single sample,
wherein the housing includes
a sample loading door that is capable of being opened and closed, and
an excitation light source that irradiates, from a side of the lens, the sample placed on the tray with excitation light for emitting fluorescent light, and
a filter turret that has a plurality of filters for limiting a wavelength used for imaging by being inserted between the sample and the lens,
wherein the excitation light source is prevented from emitting light in a case where the sample loading door is opened, and
wherein driving of the filter turret is stopped in a case where the sample loading door is opened,
wherein a live view mode, in which the plane light source is turned off and a moving image of the sample placed on the tray is captured and is displayed on a display, is provided.
2. The sample imaging apparatus according to claim 1,
wherein the plane light source is prevented from emitting light in a case where the sample loading door is opened.
3. The sample imaging apparatus according to claim 1, wherein the imaging control unit adjusts the focal length of the lens and performs imaging, a plurality of times, in a case of imaging the single sample.
4. The sample imaging apparatus according to claim 1, further comprising:
a light blocking plate that is capable of being inserted and removed between the tray and the plane light source;
a light blocking plate detection unit that detects insertion and removal of the light blocking plate; and
a control unit that prevents the plane light source from emitting light in a case where the light blocking plate is inserted between the tray and the plane light source.
5. The sample imaging apparatus according to claim 1, further comprising:
a light blocking plate that is capable of being inserted and removed between the tray and the plane light source;
a light blocking plate detection unit that detects insertion and removal of the light blocking plate,
wherein in a case where the light blocking plate is removed from between the tray and the plane light source, the excitation light source is prevented from emitting light, and in a case where the light blocking plate is inserted between the tray and the plane light source, the excitation light source is permitted to emit light.
6. The sample imaging apparatus according to claim 1, further comprising:
a light blocking plate that is capable of being inserted and removed between the tray and the plane light source;
a light blocking plate detection unit that detects insertion and removal of the light blocking plate,
wherein in a case where the light blocking plate is removed from between the tray and the plane light source and imaging of the sample using the fluorescent light is intended to be performed, a warning is notified.
7. The sample imaging apparatus according to claim 1,
wherein the live view mode is executed in a case where the sample loading door is opened.
8. The sample imaging apparatus according to claim 1,
wherein in a case where the sample loading door is opened and the tray is set, the live view mode is executed until the sample loading door is closed.
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